Regression Of Neurological Disorders Research Articles

Electroacupuncture Inhibits Neuroinflammation Induced by Astrocytic Necroptosis Through RIP1/MLKL/TLR4 Pathway in a Mouse Model of Spinal Cord Injury.

Astrocytic necroptosis plays an essential role in the progression and regression of neurological disorders, which contributes to the neuroinflammation and disrupts neuronal regeneration and remyelination of severed axons. Electroacupuncture (EA), an effective therapeutic efficacy against spinal cord injury (SCI), has been proved to reduce neuronal cell apoptosis, inhibit inflammation, and prompt neural stem cell proliferation and differentiations. However, there have been few reports on whether EA regulate astrocytic necroptosis in SCI model. To investigate the effects of EA on astrocytic necroptosis and the mechanisms involved in the inhibition of astrocytic necroptosis after SCI in mice by EA, 8-week-old female C57BL/6 mice were subjected to SCI surgery and randomly divided into EA and SCI groups. Mice receiving sham surgery were included as sham group. "Jiaji" was selected as points for EA treatment, 10min/day for 14days. The invitro data revealed that EA treatment significantly improved the nervous function and pathological changes after SCI. EA also reduced the number of GFAP/P-MLKL, GFAP/MLKL, GFAP/HMGB1, and Iba1/HMGB1 co-positive cells and inhibited the expressions of IL-6, IL-1β, and IL-33. The results indicate a significant reduction in inflammatory reaction and astrocytic necroptosis in mice with SCI by EA. Additionally, the expressions of RIP1, MLKL, and TLR4, which are associated with necroptosis, were found to be downregulated by EA. In this study, we confirmed that EA can inhibit neuroinflammation by reducing astrocytic necroptosis through downregulation of RIP1/MLKL/TLR4 pathway in mice with SCI.

Hyperbaric oxygenation therapy in treatment of traumatic spinal cord injury: a pilot study

Spinal cord traumatic injury as resulting persistent movement and sensory disorders is one of the most disabling consequences of traumatic factor impact on the human body. Despite a large number of experimental and clinical studies aimed at developing methods for restoring lost functions, there is no acceptable solution to the problem. One of the promising areas in the treatment and rehabilitation of this category of patients is the use of hyperbaric oxygenation (HBO). Experimental models have shown that HBO has a neuroprotective effect in spinal cord injury, but the results of clinical application of the method are still controversial. Objective: to determine the effectiveness of HBO in the complex therapy of victims with traumatic spinal cord injury and the feasibility of further study of this area. Materials and Methods: Study design is a pilot observational retrospective “case – control”. The database of patients with spinal cord injury who were hospitalized at Romodanov Neurosurgery Institute in the period from 2010 to 2020 were used for the analysis. When selecting a control for each clinical case, the following factors were considered: gender, age, circumstances of injury, type of damage to the osteoligamentous apparatus, level of neurological deficit, degree of damage and compression of the spinal cord, time elapsed from the moment of injury to surgery. 28 "case ‒ control" pairs were analyzed. The main criterion for therapy effectiveness was the change in the functional class according to the ASIA scale. Results. Positive dynamics was registered in 57% of victims, including in the group of patients receiving HBO therapy - in 71%, in the control group - in 43%. HBO therapy in the postoperative period significantly affects the dynamics of regression of neurological disorders (p=0.0295). The odds ratio is 3.333 (95% confidence interval - 1.098‒10.116, p=0.0335). The calculation of the odds ratio, adjusted for additional analyzed factors, showed a more pronounced efficiency - 4.519 (95% confidence interval - 1.279‒15.962, p=0.0192). Conclusions. The obtained results indicate that usage of HBO as a method of complex therapy for traumatic spinal cord injury is promising for further study in order to determine the effectiveness of the method, the optimal timing of treatment initiation in the postoperative period and its duration.

Neuropathic pain as a predictor of neurological disorders regression in patients with spinal cord traumatic injury

Background. Neuropathic pain is one of the principal secondary complications of spinal cord injury. The biological role of neuropathic pain has not been established yet. This type of pain is formed directly in the area of the spinal cord injury; therefore, it can be assumed that its intensity may characterize both degenerative and reparative processes. The aim of this work is to assess the possible relationship between the intensity of neuropathic pain in patients with spinal cord injury at cervical subaxial spine and the dynamics of neurological disorder regression. Materials and methods. We have performed a retrospective analysis of patients referred to outpatient department of the Romodanov Neurosurgery Institute of National Academy of Medical Sciences of Ukraine in the period from 2010 to 2020 after a surgical treatment of subaxial cervical spine traumatic injury. The extent of neurological disorders and the intensity of neuropathic pain were assessed within 5–7 and 11–13 months after surgery. Results. All 102 patients selected for analysis were divided into three groups depending on the intensity of the registered pain sensations: 1) absence of constant pain sensations — 19.6 % of subjects, 2)moderate pain— 56.9 %, 3) severe neuropathic pain — 23.5 %. In the first group, the regression of neurological disorders was 3.5 (95% confidence interval (CI) 2.15–6.15), in the second — 25.0 (95% CI 24.14–29.58), in the third — 13.0 (95% CI 10.87–16.55). The differences are statistically significant (χ2 = 60.4, df = 2, p < 0.0001). In patients with severe neurological disorders, the dynamics of recovery did not correlate with the pain intensity. With ASIA B, the dynamics of group 1 was 8.5 (95% CI 10.56–27.56), of group 2— 15.0 (95% CI 13.41–18.41), of group 3 — 10.5 (95% CI 7.45–14.89). With ASIA C functional class, the difference is even more pronounced: in group 1, the median was 8.0 (95% CI 0.83–20.83), in group 2 — 32.0 (95% CI 25.41–36.86), in group 3 — 15.5 (95% CI 10.27–27.4). With ASIA D, a similar trend was observed. Conclusions. The worst regression of neurological disorders is observed in patients without clinically significant pain, the best results of neurological dysfunction recovery are found in patients with mode rate neuropathic pain.

Surgical management of traumatic irreducible spondyloptosis of thoracolumbar junction

Introduction. The thoracolumbar junction is the most common location of traumatic spinal injuries. It accounts for 50-60% of all thoracic and lumbar spine injuries. Spondyloptosis is rather rare, but one of the most severe types of traumatic injury, that is characterized by a severe damage of spinal axis in one or more planes. Traumatic spondyloptosis is classified as reducible and irreducible, depending on the possibility of intraoperative restoration of the spinal axis without resection of the damaged vertebra. Objective. To determine the optimal surgical technique for traumatic irreducible spondyloptosis of thoracolumbar junction. Materials and methods. A retrospective analysis of the patients’ database treated at the Romodanov Neurosurgery Institute, Ukraine was performed over the past 4 years (2017 to 2020) to identify all cases with traumatic irreducible spondyloptosis of the thoracolumbar junction. Results. Treatment outcomes of five patients aged 18 to 52 years (mean age 31.2 years) were analyzed. The minimum period from the moment of injury to surgery was 14 days, the maximum was 3 months and 2 days (on average 42.2 days). At the time of admission all patients had a neurological deficit that corresponds to the functional class A on the American spine injury associatin ASIA scale of severity of spinal cord injury. The TLICS (Thoracolumbar injury classification and severity) score was 8 points. All the patients had the injury of lateral spondyloptosis: in three cases as an isolated displacement only in the coronal plane, in two – as a combined one - in the coronal and sagittal plane. Surgical intervention in all cases was performed from the posterior approach. As a body replacement system in 2 patients, a vertical cylindrical implant (Mesh) was used, in 3 patients - a telescopic body replacing implant. The method of bicortical implantation of pedicle screws was applied. The transpedicular system was strengthened by two cross links of the rod-to-rod type. In all cases the restoration of spinal axis was achieved in both the coronal and sagittal planes. Follow-up examinations were carried out 2, 6 and 12-18 months of the postoperative period. Regression of neurological disorders was registered in two patients, in one case to ASIA B, in the other to ASIA C. Conclusions. Isolated posterior approach has demonstrated high efficacy in the surgical management of traumatic irreducible spondyloptosis of the thoracolumbar junction both in restoring the axis of the spine and in ensuring the stability of fusion.

Suprasellar cyst after subarachnoid intraventricular hemorrhage and ventriculoperitoneal shunt implantation

The objective is to describe a rare clinical case of a suprasellar cyst formed after implantation of a ventriculoperitoneal shunt. Clinical observation . A female patient, 51 years, suffered non-traumatic subarachnoid intraventricular hemorrhage, acute obstructive and subsequently normal pressure hydrocephalus requiring implantation of a ventriculoperitoneal shunt. In several years, the patient developed a suprasellar cyst manifesting through cerebral symptoms. Results . Two (2) surgeries were performed. During the 1st surgical intervention, endoscopic ventriculostomy was performed with positive outcome (full regression of the symptoms). After 6 months, cyst recurrence was confirmed, and endoscopic ventriculocystocisternostomy with replacement of a low pressure pump with intermediate pressure pump was performed. Full regression of neurological disorders was observed; magnetic resonance imaging did not show cyst recurrence 6 months after the 2 nd surgery. Conclusion . This clinical observation expands our knowledge on the diversity of mechanisms of suprasellar arachnoid cyst formation and demonstrated effectiveness of one of the techniques for prevention of cyst formation in the context of ventriculoperitoneal shunt.

Risk of Unsatisfactory Functional Outcome of Stroke in Patients with Clinical Manifestation of Persistent Viral Infection

Acute cerebrovascular disorders represent up to 75–85 % of strokes inUkraine. The wide spread of herpesvirus infection in developing countries (with a prevalence of 35–40 %), as well as influenza virus, requires consideration of the viral risk factor of stroke for prognostic purposes.The objective: to study the influence of the most common types of viral infection: the family of herpesviruses and influenza virus on the neurological and one-year functional outcome of stroke and to determine the predictors of unsatisfactory recovery of patients.Materials and methods. In the period from 2016–2020, on the basis of the neurological departments ofAlexanderHospital andClinicalHospital № 4 we performed research on the presence of herpes viruses. 70 patients with ischemic stroke with moderate and severe neurological disorders were examined, in whom herpes and influenza viruses were detected in the blood (the main group) within 2 weeks before hospitalization against the background of viral manifestation. The comparison group consisted of 220 patients without clinical signs of viral manifestations were compared with the main group by stroke severity, average age and gender. The severity of neurological disorders was assessed by the NIHSS scale. Functional recovery was assessed by the Barthel index. The presence of viral infection (family of herpesviruses and influenza virus) was studied using polymerase chain reaction.Results. HSV1 DNA was detected in 43 (61.4 %) cases, HSV2 – in 30 (42.9 %), EBV4 – in 19 (27.1 %), CMV5 – in 18 (25.7 %), HNV6 – in 27 (38.6 %), Influenza RNA – in 16 (22.9 %). Only one type of virus was present in 21 (30.0 %) patients, two types of viruses were identified in 31 (44.3 %), three or more types of viruses – in 18 (25.7 %). In the presence of viral infection, the relative risk of unsatisfactory recovery of neurological functions in the main group increases 1.99 times relative to the comparison group: RR=1.99 (95 % CI: 1.60–2.48). The presence of viral infection predicted unsatisfactory recovery with a sensitivity of 74.3 %, a specificity of 62.7 % and an area under the curve ROC=0.69. There was a negative correlation between increasing the number of virus types in patients and the lack of neurological improvement: r=0.370 (p=0.002). The presence of viral infection significantly increased the risk of moderate and severe disability one year after stroke, the relative risk of disability in patients of the main group relative to patients of comparison group was: RR=1,668 (95 % CI: 1,256–2,214), and IB score according to the linear regression analysis inversely depended on the number of viruses in patients, linear R2=0.423 (correlation coefficient r=–0.660). In the presence of two types of viruses in the blood, the probability of unsatisfactory recovery increased – 1.5 times (RR=1,562; 95 % CI: 1,064–2,265), three or more viruses 2.5 times (RR=2,511; 95 % CI: 1,888–3,340). One year after stroke, there was a significant correlation between lower IB score and the presence of HSV1 in associations: r=0.323; CMV: r=0.351; EBV: r=0.430. If there are at least 2 types of viruses in the blood, in particular HSV1+CMV and HHV6+CMV, the relative risk of PI and TI increases 2.9 times.Conclusions. The presence of a viral infection significantly increases the risk of unsatisfactory regression of neurological disorders, allows to predict poor neurological recovery with a sufficiently high sensitivity and specificity. In patients with viral manifestations and detection of the virus in the blood, functional recovery one year after stroke is significantly worse than in patients without it; this applies to a lower mean score of IB and the percentage of patients with minimal limitation of function. When the number of persistent viruses increases to two or more, the relative risk of PI and TI increases one year after stroke, with the highest rate in the presence of EBV and CMV associations. If there are at least 2 types of viruses in the blood, in particular HSV1+CMV, HHV6+CMV, HSV1+EBV the relative risk of PI and TI increases 2.9 times.

Исследование механизма нейропротективного действия пептидного препарата Семакс в мозге крыс в условиях ишемии-реперфузии

Синтетический пептид АКТГ(4-7)PGP ускоряет регресс неврологических нарушений при ишемическом инсульте, однако молекулярные механизмы его действия полностью не известны. На модели полуторачасовой окклюзии средней мозговой артерии крыс был проведен анализ влияния пептида на экспрессию ряда генов и белков, вовлеченных в сигнальные пути, приводящие к воспалению и гибели клеток в условиях ишемии-реперфузии. Показано, что пептид через 24 ч от начала окклюзии снижает повышенный при ишемии уровень экспрессии в ишемизированной ткани мозга крыс мРНК провоспалительных цитокинов и хемокинов IL-1α, IL-1β, IL-6, TNF-α, Cxcl2 и Ccl3. Пептид снижал повышенные при ишемии уровни экспрессии белков металлопротеиназы ММР-9, транскрипционного фактора c-Fos, активных JNK киназ и предотвращал ишемическое снижение уровня активного транскрипционного фактора CREB. The synthetic peptide ACTH (4-7) PGP accelerates the regression of neurological disorders in ischemic stroke, but the molecular mechanisms of its action are not completely known. On the model of an hour and a half occlusion of the rat middle cerebral artery, an analysis was made of the effect of the peptide on the expression of a number of genes and proteins involved in signaling pathways leading to inflammation and cell death under conditions of ischemia-reperfusion. It was shown that the peptide 24 hours after the onset of occlusion reduces the level of expression of mRNA of pro-inflammatory cytokines and chemokines IL-1α, IL-1β, IL-6, TNF-α, Cxcl2 and Ccl3 in ischemic brain tissue. The peptide decreased the levels of expression of proteins metalloproteinase MMP-9, transcription factor c-Fos, active JNK kinases wich were increased under ischemia, and prevented ischemic decrease in the level of active transcription factor CREB.

Peculiarities of Spondylitis in the Patients Undergoing Program Hemodialysis (Case Report)

Relevance. The surgical treatment of spinal diseases and injuries in the patients on hemodialysis is one of the most complicated problems of the spine surgery, since such a surgery is associated with an increased risk of infectious complications and perioperative mortality. The case description. A 59-year-old female came to the clinic complaining back pain. Th8-9 vertebrae spondylitis complicated by an epidural and paravertebral abscess with pertinent neurological disorders and bilateral pneumonia were diagnosed. The patient had been on hemodialysis for 18 years due to the end-stage chronic kidney disease complicated by uremic osteodystrophy. The surgical debridement and stabilization of the spine were performed in one stage posterior approach using a titanium mesh implant in combination with autologous bone and posterior instrumentation. A regression of neurological disorders and the pain syndrome relief were achieved. In the late postoperative period, the instability of the posterior fixation developed twice, requiring restabilization. Within the following 3.5 years after the operation, the pain syndrome had not returned. Conclusion. The presence of equipment for hemodialysis and a multidisciplinary approach allow to achieve the positive results in the surgical treatment of inflammatory diseases of the spine in the patients with endstage chronic kidney disease.

The classifications of subaxial cervical spine traumatic injuries. Part 1. General principles

Cervical spine and spinal cord injury is a significant medical and socio-economic problem of modern society. Ongoing urbanization, the development of high-speed modes of transport and the intensification of military conflicts lead to a progressive increase in the number of victims with this pathology. At the same time, unlike several other socially significant diseases, the category of the most employable population suffers from spinal injuries. Achievements of modern medicine to a much greater extent contribute to reducing the mortality of patients, rather than regression of neurological disorders. The usage of new diagnostic methods for neuroimaging and expensive surgical instruments, the continuous improvement of rehabilitation treatment of patients with spinal cord injury determine the progressively increasing costs for medical and social life support expenses. A large number of experimental and clinical studies, improvement of methods for surgical correction and stabilization of the damaged vertebral motor segment undoubtedly dictate certain changes in the tactics of treatment. The classification of traumatic spinal injuries is of key importance in determining the approaches, timing and volume of surgical intervention. Following the care algorithms helps to minimize the negative effects of traumatic damage to both the spine and the spinal cord and contributes to the maximum possible recovery of neurological functions. The last few decades have been characterized by the gradual replacement of the previously widely used “morphological” classifications of traumatic injuries of the cervical spine to “clinical” ones, based on an analysis of some heterogeneous factors determining treatment tactics. The first part of the review deals with a detailed description of the main criteria used in developing modern “clinical” classifications of subaxial cervical spine traumatic injuries. Besides, modern views on imaging methods and algorithms for determining the need to perform diagnostic procedures at primary hospitalization in patients with suspected cervical spine traumatic injury are presented.

Surgical treatment of lower lumbar spine pathology in children and adolescents

Introduction. Analysis of the modern literature shows that the number of children complaining of low back pain of varying intensity in the spine increases annually. Publications on the surgical treatment of juvenile osteochondrosis were scarce. Currently, there are no algorithms for choosing a surgical treatment for children and adolescents with lumbar spine pathology, particularly high-grade listhesis, methods and terms of surgical treatment, and the use of reduction maneuvers remain debatable. There are no high-quality evidence studies.
 Aim. This study aimed to summarize the experience of treatment of children and adolescents with pathology of the lower lumbar spine.
 Material and methods. We performed a retrospective analysis of the treatment outcomes in patients with lower lumbar spine pathology who were younger than 18 years and who underwent surgery in the Neurosurgical Department No. 2 of the Tsiv’yan Novosibirsk Research Institute of Traumatology and Orthopedics between 2008 and 2018. The mean age of the patients was 15.5 years. We structured pathologies and interventions in children and adolescents and evaluated the clinical and radiological outcomes of treatment and the rate of intraoperative and postoperative complications.
 Results and discussion. From 2008 to 2018, 11,428 patients with degenerative spine disease and isthmic/dysplastic spondylolisthesis underwent surgery at the Neurosurgical Department No. 2. Of these, 55 (0.5%) patients were younger than 18 years. In all patients, surgical treatment led to pain relief and physical activity recovery. Decompression/stabilization surgery through the posterior approach enabled formation of an artificial block in 100% of cases. The rate of surgical treatment complications was 8.6% and 28.6% in children and adolescents with herniated lumbar intervertebral discs and spondylolisthesis, respectively.
 Conclusion. Surgical treatment of children and adolescents with pathology of the lower lumbar spine demonstrated an excellent clinical outcome. Disc herniation did not recur 4.9 years after decompression surgery for herniated lumbar intervertebral discs. Decompression/stabilization surgery through the posterior approach in children and adolescents with spondylolisthesis facilitated abolition of pain, regression of neurological disorders, full recovery of physical activity, and formation of a reliable artificial block. Potential complications were resolved without consequences and did not downplay the importance of surgical techniques in the treatment of this group of patients.

THE INFLUENCE OF TIMING OF SURGICAL TREATMENT OF CHILDREN WITH SPINAL CORD INJURY ON THE DYNAMICS OF NEUROLOGICAL DISORDERS

Objective. To assess the dynamics of neurological disorders in children with spine and spinal cord trauma in the thoracic and thoracolumbar spine, depending on the timing of surgery and the severity of spinal cord injury. Material and Methods . A total of 36 children aged 3 to 17 years were operated on for injuries to the thoracic spine and thoracolumbar junction accompanied by neurological deficit. Thoracic spine was damaged in 16 (44.4 %), thoracolumbar junction - in 20 (55.6 %) patients. Patients were divided into four groups based on time to surgery. Spinal bone lesions were assessed according to Magerl’s classification, and neurological disorders - to the ASIA scale. Results . Long-term results were followed for 5 years in all patients. Neurological function improvements in patients of Group 1 were observed in 1-2 days after surgery, Group 2 - in 2-3 days, Group 3 - in 5-7 days, and Group 4 - in 4-5 months. In Group 1 positive dynamics was observed as significant regression of sensory disorders, in Group 2 - as complete regression of neurological deficit in 2 patients, in Group 3 - as transition from C to D grade in 4 patients, from B to D grade in 2 patients, and 2 children had no regression. In Group 4 a regression of neurological disorders from B to C grade was observed in 6 children in 2-3 years, and 10 patients (A grade) had no improvement in neurological status. Conclusion . Complete and rapid recovery of neurological functions in children with complicated fractures of thoracic and thoracolumbar spine is observed after surgical treatment performed within the first 6-12 hours after injury, when neurological deficit is mainly caused by compression of the spinal cord and its elements, and secondary circulatory and pathological changes have not yet expressed.

Efficacy of valdoxan in the prevention and treatment of post-stroke depression

The efficacy of valdoxan (agomelatine) used to prevent and treat post-stroke depression was analyzed. The study enrolled 49 patients (21 men and 28 women; mean age 61+5.5years) in the acute period of ischemic stroke in different vascular basins (a study group). A control group included 50 patients (24 men and 26 women; mean age 64+4.8 years) who were comparable with the study group of patients and who did not receive valdoxan. The duration of a follow-up was 6 months. During valdoxan therapy, there were better changes in recovery with a rapider regression of neurological disorders in patients with moderate stroke as compared with the control group (according to the National Institute of Health Stroke Scale (NIHSS). The administration of valdoxan prevents depression, sleep disorders, pain syndromes, and cognitive impairments in the acute and early rehabilitation period of stroke.

Giant Cell Tumorsof the Spine in Children

Objective. To study clinical and radiological signs, and outcomes of treatment of giant cell tumor (GCT) of the spine in children. Material and Methods. Clinical and radiological features, therapeutic approach, and results of treatment of six children aged from 10 to 15 years with GCT of the spine were analyzed. Results. All patients underwent radical reconstruction of the spine with singlestep tumor removal. Shortterm surgery outcomes demonstrate reduction of pain, regression of neurological disorders, and restoration of the spine support. Five children have an ordinary lifestyle without subjective complaints. Recurrence of GCT was diagnosed in one case. Conclusion. Clinical and radiological signs of GCT are not specific in comparison with other monosegmental destructivelytic vertebral lesions. Pain and neurological disorders are typical clinical manifestations of GCT of the spine. СТ and MRI examinations are highly informative methods for determination of the tumor dissemination and aggressiveness, and percutaneous biopsy – for its preoperative verification. Radical GCT removal with spine support restoration is the only justified method for GCT treatment in children.

Clinical experience with ceraxon used in ischemic stroke

Citicoline (Ceraxon) is a neuroprotective agent used in acute ischemic stroke (IS) and chronic cerebrovascular diseases. The efficiency and safety of Ceraxon intravenously in a dose of2000 mg/day for 10 days, then orally for 35 days with evaluation of its effect on cognitive functions were studied in 24 patients (13 men, 11 women; mean age 68.2+9.3 years) with IS. During treatment, none of the patients died or developed recurrent stroke, myocardial infarction, or other vascular events. A gradual regression of neurological disorders and a lower degree of disability were observed in most patients (18/24). Ceraxon was found to have a positive effect on cognitive function and their improvement on day 45 after disease onset. The findings agree with the results of the multicenter studies showing the efficacy and safety of citicoline in IS.